CN108289804A

CN108289804A - Metal amino acid complex for bacterial accumulation

Info

Publication number: CN108289804A
Application number: CN201680071094.9A
Authority: CN
Inventors: 林赛·谢弗-科尔贝洛; 丽萨·马努斯
Original assignee: Colgate Palmolive Co
Current assignee: Colgate Palmolive Co
Priority date: 2015-12-07
Filing date: 2016-12-05
Publication date: 2018-07-17
Anticipated expiration: 2036-12-05
Also published as: MX2018006820A; US20170157013A1; EP3386466B1; AU2016367080B2; AU2016367080A1; EP3386466A1; WO2017100116A1; CN108289804B

Abstract

Disclosed herein is the methods of the aggregation and/or immune clearance of the oral care composition used comprising metal amino acid complex promotion oral bacteria.

Description

Metal amino acid complex for bacterial accumulation

The cross reference of related application

The U.S. Patent Application Serial Number 14/960,960 that patent application claims were submitted on December 7th, 2015 it is preferential Power, the full content of the U.S. Patent application are hereby incorporated herein by.

Background technology

Complex compound between metal ion and amino acid is known.Some of them, especially bivalent metal ion and alkali Complex compound between acidic amino acid sees purposes in field of oral care because it treats the ability of dental hypersensitiveness. Have found bis- (the lysine)-zinc of certain complex compounds such as halogenation, bis- (the arginine)-zinc of halogenation and halogenation (trimethylglycine) zinc shape At stabilization, uniform aqueous solution, the aqueous solution can make zinc hydroxide, zinc oxide and other zinc species heavy under certain conditions It forms sediment.The precipitation of this insoluble salt enables the oral care composition comprising these complex compounds effectively to block transmission allergy The dentinal tubule for the tooth that disease is felt.

The salt of bivalent metal ion, especially zinc, stannous and copper is commonly referred to as antiseptic.Especially zinc salt and tin salt It is used for oral care composition because of its anti-plaque, anti-calculus and anti-stench effect, the effect to arise from the zinc ion of connection With the bioavilability of the enhancing of oral surfaces interaction.The example of the zinc complex used in the past includes zinc oxide, lemon Sour zinc and zinc chloride.The effect of these salt and tolerance due in astringent taste, aesthetic appearance and these preparations for feeling at point it Between interaction and change.

It is the important letter that immune system is used to that harmful bacteria to be promoted to remove in the aggregation of people (or other animals) Endophytic bacteria Number.Although each bacterial cell is difficult to detect and remove for immune system, the aggregation of bigger is much effectively targeted For removing and removing.In fact, antibody is by causing bacterial accumulation, therefore label by an important mechanisms of its running They are used for through the intake by phagocytic immunocyte.Natural and synthesis various molecules have been described as promoting bacterium poly- Collection, and beneficial antimicrobial effect therefore can be played in human body.

Free metal ion includes that zinc ion has proven to promote bacterial accumulation, but this is considered reflecting to the non-of biomembrane Specific effect.In fact, this effect is confirmed also for some eukaryocytes.

The purposes and various gold that although prior art discloses various metal amino acid complexes in oral cavity composition Belong to the purposes that ion is used for bacterial accumulation, but there is still a need for the other composition and method for providing selective bacterial accumulation, it is described Selective bacterial accumulation can have benefit in oral care composition.

Invention content

Have now been found that certain bivalent metal ions can form highly soluble complex compound with amino acid, and these are complexed Object can effectively and selectively promote the aggregation of bacterium.Preferred complex compound is in zinc (II) ion or copper (II) ion and amino It is formed between acid, especially basic amino acid (such as lysine or arginine).

In some embodiments, including zinc and amino acid and the complex compound of optional anion and/or oxygen formed it is solvable Property cationic portion, successively again can be with halide or other anion forming salts.Compared with the preparation with insoluble zinc salt, While the bacterial accumulation for promoting to improve, including the preparation of zinc-amino acid complex does not show and uses soluble Zn The relevant poor taste of conventional zinc-base oral care product of salt and mouthfeel, the delivering of weak fluoride and weak blistering and cleaning.

In a particular embodiment, zinc-amino acid complex is zinc-lysine-HCl complex compounds, such as is appointed as ZLC Complex compound, can be formed by the mixture of zinc oxide and lysine hydrochloride.ZLC has chemical constitution [Zn (C₆H₁₄N₂O₂)₂Cl ]⁺Cl^-, and may be present in cationic cation ([Zn (C₆H₁₄N₂O₂)₂Cl]⁺) and the solution of cl anion in, or can be Solid salt such as crystal, optionally in the form of monohydrate or dihydrate.This ZLC complex compounds are in WO 2014/ 098822, it is disclosed in WO 2014/098824, WO 2014/098825 and WO 2014/098826, the respective content of patent It is incorporated hereby herein.

Present disclosure thus provides oral care composition, such as mouthwash, buccal cavity gel or dentifrice composition, It includes the metal-aminoacid complexes for promoting oral bacteria to assemble, such as zinc-amino acid complex, such as zinc-to rely ammonia Acid-chloride complex, such as ZLC.Composition is also optionally including fluoride source and/or other phosphate source.It is described Composition can be prepared in suitable oral care formulations, such as conventional dentifrice, buccal cavity gel or water-based of gargling, such as wrap Containing one or more abrasive materials, surfactant, foaming agent, vitamin, polymer, enzyme, moisturizer, thickener, antimicrobial, Preservative, seasoning and/or colorant.

Include metal-aminoacid complex such as zinc-amino acid complex the present disclosure also provides using, such as The oral care composition of zinc-lysine-chloride complex (ZLC) is to promote the method for the immune clearance of oral bacteria.This It can lead to the multiple advantageous effect to oral hygiene and oral health, including reduce and inhibit the acid attack of enamel, cleaning tooth Tooth reduces biomembrane and patch, the formation for reducing gingivitis, inhibition decayed tooth and saprodontia that bacterium generates.This method includes that incite somebody to action this The composition of disclosure is applied to tooth.

Other suitable application areas of the present invention will become obvious from the detailed description provided hereinafter.It will be appreciated that in detail Although illustrating and particular instance indicating the preferred embodiment of the present invention, it is intended only for the purpose of explanation and is not intended to limit this hair Bright range.

Specific implementation mode

Following description of preferred embodiments is merely exemplary in itself, and is in no way intended to limit the present invention, sheet The application of invention or purposes.

In one embodiment, this disclosure provides the sides of the aggregation and/or immune clearance that promote oral bacteria Method (method 1), the method includes including the oral care composition of metal-aminoacid complex to personal oral administration (composition 1).In some embodiments, method 1 effectively treatment mouth disease, illness and situation, for example, gingivitis, periodontitis, Halitosis, dental cavity formation, enamel corrodes and mouth infection (such as thrush), or destroys plaque and bacterial biof iotalm It is formed.

In the second embodiment, this disclosure provides treatment mouth disease, the method (methods of illness or situation 2), the method includes the oral care composition (combination comprising metal-aminoacid complex is applied to patient in need Object 1), to promote the aggregation and/or immune clearance of oral bacteria.In a particular embodiment, the patient is with mouth disease, disease Disease or situation, such as gingivitis, periodontitis, halitosis, dental cavity formation, enamel corrode and/or mouth infection (such as oral candidiasis Bacterium disease).

In a particular embodiment, method 1 or method 2 include the application of oral care composition, wherein the oral care Composition is：

1.1. composition 1, wherein metal-aminoacid complex include bivalent metal ion (such as zinc (II) or copper (II))。

1.2. composition 1 or 1.1, wherein metal-aminoacid complex include zinc (II) ion.

1.3. composition 1 or 1.1, wherein metal-aminoacid complex include copper (II) ion.

1.4. composition 1 or 1.1-1.3, wherein amino acid be natural amino acid with L- or D-shaped formula or with L- or The modified amino acid (such as N- Alkylation of Amino Acids, such as the mono-, two- or alkylated amino acid of three-N-) of D-shaped formula.

1.5. composition 1 or 1.1-1.4, wherein amino acid be selected from lysine, glycine, tetramethyl glycine (TMG) and Arginine, with free or orally acceptable acid addition salt form thereof, such as hydrochloride form.

1.6. composition 1 or 1.1-1.5, wherein amino acid are the basic amine groups with free or orally acceptable salt form Acid, such as arginine or lysine.

1.7. any one of aforementioned composition also includes the halide (example with metal ion and amino acid ions binding Such as chloride, bromide or fluoride).

1.8. any one of aforementioned composition, wherein metal ion：The molar ratio of amino acid is 3: 1 to 1: 5, for example, about 1: 2, and metal ion：The molar ratio of halide is 3: 1 to 1: 3, for example, about 1: 2.

1.9. any one of aforementioned composition, wherein metal ion-amino acid complex are applying in whole or in part It is formed in situ after composition.

1.10. any one of aforementioned composition, wherein metal ion-amino acid complex are being prepared in whole or in part It is formed in situ after composition.

1.11. any one of aforementioned composition, wherein amino acid are lysine.

1.12. any one of aforementioned composition, wherein metal ion-amino acid complex are zinc-Lysine Complexes.

1.13. any one of aforementioned composition, wherein metal ion (such as zinc) are by based on the weight of composition 0.05 To 10%, at least 0.1 optionally based on the weight of composition, at least 0.2, at least 0.3, at least 0.4, at least 0.5, at least 1, at least 2, at least 3 or at least 4 until 10%, such as the amount of by weight about 1-3%, for example, about 2-2.7% exist.

1.14. any one of aforementioned composition, wherein amino acid are by 0.05 to 30% based on the weight of composition, optionally By weight at least 0.1, at least 0.2, at least 0.3, at least 0.4, at least 0.5, at least 1, at least 2, at least 3, at least 4, at least 5, at least 10, at least 15, at least 20 until 30%, such as the amount of by weight about 1-10% exists.

1.15. any one of aforementioned composition, the wherein molar ratio of zinc/amino acid be 2: 1 to 1: 4, optionally 1: 1 to 1: 4,1: 2 to 1: 4,1: 3 to 1: 4,2: 1 to 1: 3,2: 1 to 1: 2 or 2: 1 to 1: 1, for example, about 1: 2 or 1: 3

1.16. any one of aforementioned composition, including the halide with zinc and amino acid ions binding, wherein halide Selected from fluorine, chlorine, bromine and its mixture.

1.17. any one of aforementioned composition, wherein zinc amino acid chelate are zinc LYSINE MONOHYDROCHLORIDE complex compound (examples Such as (ZnLys₂Cl)⁺Cl^-Or (ZnLys₃)²⁺Cl₂) or zinc ARGININE HYDROCHLORIDE complex compound.

1.18. any one of aforementioned composition, wherein zinc amino acid chelate are zinc LYSINE MONOHYDROCHLORIDE complex compounds, Such as ZLC, such as with chemical constitution [Zn (CC₆H₁₄N₂O₂)₂Cl]⁺Cl^-Zinc LYSINE MONOHYDROCHLORIDE complex compound, or in cation Type cation (such as [Zn (C₆H₁₄N₂O₂)₂Cl]⁺) and the solution of cl anion in, or with solid salt form, such as crystal shape Formula, optionally with monohydrate or dihydrate form.

1.19. with toothpaste, the aforementioned combinatorial of gel, mouthwash, powder, emulsifiable paste, item (such as film) or gum formats Any one of object.

1.20. in the aforementioned composition in orally acceptable matrix, such as mouthwash, gel or denfifrice matrix It is any.

1.21. any one of the aforementioned composition in the form of denfifrice, such as wherein metal-aminoacid complex (example Such as zinc-lysine, zinc-arginine or copper-Lysine Complex) it is present in denfifrice matrix with effective quantity, such as in an amount of from The metal of 0.5-4% (such as zinc) by weight, for example, by weight about 1-3% metal (such as zinc).

1.22. any one of the aforementioned composition in the form of denfifrice, wherein denfifrice matrix include abrasive material, such as two The effective quantity of silica abrasive, such as 10-30%, for example, about 20%.

1.23. with any one of aforementioned composition of mouthwash form, such as wherein metal-aminoacid complex (example Such as zinc-lysine, zinc-arginine or copper-Lysine Complex) exist with effective quantity, such as in an amount of from the weight by composition Meter 0.1 to 2%, or based on the weight of composition 0.5 to 1.5% or 1-1.3%, or wherein metal-aminoacid complex with The zinc of the 0.01-0.5% based on the weight of composition, such as the 0.01-0.25% based on the weight of composition or 0.014- are provided The amount of 0.14% zinc exists.

1.24. any one of aforementioned composition also includes a effective amount of fluoride sources, such as provides 50 to 3000ppm Fluoride.

1.25. any one of aforementioned composition includes also a effective amount of fluoride, for example, the wherein described fluoride is Selected from stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, prodan, ammonium fluosilicate, amine fluoride (such as N '-octadecanes Base trimethylene diamine-N, N, N '-three (2- ethyl alcohol)-bifluoride hydrogen), ammonium fluoride, titanium fluoride, hexafluoro sulfate and combinations thereof Salt.

1.26. any one of aforementioned composition, including a effective amount of one or more alkali metal phosphates, such as sodium Salt, sylvite or calcium salt, such as selected from alkali metal dibasic phosphate and alkali metal pyrophosphate, for example, selected from disodium hydrogen phosphate, Dipotassium hydrogen phosphate, dicalcium phosphate, dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, trimerization phosphorus Any mixture in sour sodium and two or more in these, such as in an amount of from the 1-20% based on the weight of composition, Such as 2-8%, for example, about 5%.

1.27. any one of aforementioned composition, including buffer such as phosphate buffer or citrate buffer, Such as sodium phosphate buffer (such as sodium dihydrogen phosphate, disodium hydrogen phosphate and/or phosphoric acid).

1.28. any one of aforementioned composition, including for example selected from glycerine, D-sorbite, propylene glycol, polyethylene glycol, The moisturizer of xylitol and its mixture, such as include the glycerine of at least 20%, such as 20-40%, such as 25-35%.

1.29. any one of aforementioned composition, including one or more surfactants, such as selected from anion, sun Ion, amphoteric ion and nonionic surfactant and its mixture, such as comprising anion surfactant, such as selected from the moon The surfactant of osmanthus base sodium sulphate, Sodium Lauryl Ether Sulphate and its mixture, for example, in an amount of from by weight about 0.3% to About 4.5%, such as 1-2% NaLSs (SLS)；And/or zwitterionic surfactant, such as glycine betaine surface-active Agent, such as Cocoamidopropyl betaine, such as in an amount of from by weight about 0.1% to about 4.5%, such as 0.5-2% cocounut oil Amido propyl betaine.

1.30. any one of aforementioned composition also includes one or more polysaccharide colloids of viscosity-adjusting agent amount, such as yellow Virgin rubber or carrageenan, silicon dioxide thickening agents and combinations thereof.

1.31. any one of aforementioned composition, including gum strip or segment.

1.32. any one of aforementioned composition also includes seasoning, fragrance and/or colorant.

1.33. any one of aforementioned composition, including a effective amount of one or more antiseptics, such as comprising under The antiseptic stated：Halogenated diphenyl ethers (such as triclosan), herb extracts and essential oil (such as Rosmarinus officinalis extract, tea extraction, Extract of magnolia, magnolol, honokiol, Thymol, menthol, eucalyptol, geraniol, carvacrol, citral, Japan cypress Phenol, catechol, gaultherolin, Epigallo-catechin gallate (EGCG), epigallocatechin, gallic acid, toothbrush tree (miswak) extract, hippophae rhamnoides), it is biguanides preservative (such as Chlorhexidine, Alexidine or Octenidine), quaternized Conjunction object (such as Cetylpyridinium Chloride (CPC), benzalkonium chloride, tetradecyl chloride pyridine (TPC), N- myristyl -4- ethylmercury chloride pyrroles Pyridine (TDEPC)), antiseptic phenols, Hexetidine, Octenidine, sanguinarine, povidone iodine, decapinol, salifluor, gold Belong to ion (such as zinc salt, such as zinc citrate, tin salt, mantoquita, molysite), sanguinarine, (such as the peroxidating of propolis and oxidant The peroxide Boratex or sodium carbonate peroxide of hydrogen, buffering), phthalic acid and its salt, single peptide acid and its salt and ester, stearic acid it is anti-bad Hematic acid ester, oleoyl sarcosine, alkyl sulfate, dioctylsulfosuccinat, salicylanilide, Domiphen bromide, decapinol, Xin Bo Alcohol and other acyclic derivatives, nicin preparations, chlorite；And it is aforementioned in any mixture；Such as include trichlorine Raw or hexadecylpyridinium chloride or magnolol or honokiol.

1.34. any one of aforementioned composition, also include brightening agent, such as selected from peroxide, metal chlorite, Perborate, percarbonate, peroxy acid, hypochlorite and combinations thereof.

1.35. any one of aforementioned composition also includes hydrogen peroxide or hydrogen peroxide source, such as urea peroxide or mistake Oxide salt or complex compound (such as peroxide phosphoric acid salt, peroxycarbonate, perborate, peroxide silicate or persulfate；Such as Peroxide phosphoric acid calcium, sodium perborate, sodium carbonate peroxide, peroxide phosphoric acid sodium and potassium peroxydisulfate)；

1.36. any one of aforementioned composition also includes interference or prevents the reagent of bacterial adhesion, for example, solbrol Or chitan.

1.37. any one of aforementioned composition also includes calcium selected from the following and phosphate source：(i) calcium-glass is compound Object, such as phosphorus sodium calcium silicate, and (ii) calcium-protein complex, such as casein phosphopeptide-amorphous calcium phosphate

1.38. any one of aforementioned composition includes also soluble calcium salt, such as selected from calcium sulfate, calcium chloride, nitric acid Calcium, calcium acetate, calcium lactate and combinations thereof.

1.39. any one of aforementioned composition also includes physiology or warp that its amount effectively reduces dental sensitivity The acceptable sylvite of mouth, such as potassium nitrate or potassium chloride.

1.40. any one of aforementioned composition, it is also poly- comprising anionic polymer, such as the anionic polymer of synthesis Carboxylate, such as wherein anionic polymer is selected from maleic anhydride or maleic acid and another polymerizable ethylenically unsaturated monomer 1: 4 to 4: 1 copolymer, such as it is about 30,000 to about 1,000 that wherein anionic polymer, which is average molecular weight (M.W.), 000, for example, about 300,000 to about 800,000 methyl vinyl ether/maleic anhydride (PVM/MA) copolymer, for example (,) it is wherein cloudy Ionomer be composition weight about 1-5%, for example, about 2%.

1.41. any one of aforementioned composition, also includes non-ionic polymers, such as polyvinylpyrrolidone (PVP), Such as linear or cross-linked pvp.

1.42. any one of aforementioned composition also includes flavorants, fragrance or seasoning.

1.43. any one of aforementioned composition, the wherein pH of composition are near neutral, such as pH 6 to pH 8, example Such as from about pH 7.

1.44. with any one of aforementioned composition of mouthwash form, wherein amino acid is lysine, and zinc and is relied Propylhomoserin, which is formed, has chemical constitution [Zn (C₆H₁₄N₂O₂)₂Cl]⁺Cl^-Zinc-lysine-chloride complex, pressed in an amount of from offer Weight meter 0.5-2%, for example, about 1% zinc, the composition also include for example in an amount of from 10-25%, for example, about guarantor of 15-20% Humectant, such as D-sorbite, propylene glycol and its mixture, such as non-moisturizer-ion surface active in an amount of from 0.1-1% Agent, such as poloxamer and sweetener, seasoning and water, such as mouthwash includes

1.45. any one of the aforementioned composition in the form of buccal cavity gel, wherein amino acid are lysine, and zinc and Lysine, which is formed, has chemical constitution [Zn (C₆H₁₄N₂O₂)₂Cl]⁺Cl^-Zinc-lysine-chloride complex, in an amount of from offer 0.1-2% by weight, for example, about 0.5% zinc, and also include for example in an amount of from 45-65%, for example, about guarantor of 50-60% Humectant, such as D-sorbite, propylene glycol and its mixture, such as derive in an amount of from the thickener of 0.1-2%, such as cellulose Object, for example, selected from carboxymethyl cellulose (CMC), trimethyl cellulose (TMC) and its mixture, sweetener and/or seasoning with And water, such as buccal cavity gel includes

In some embodiments, the oral bacteria assembled by purposes disclosed herein and method includes mucus actinomyces (A.viscous), Lactobacillus casei (L.casei), Streptococcus oralis (S.oralis), small veillonellasp (V.parvula) With it is one or more in Fusobacterium nucleatum (F.nucleatum).In some embodiments, purposes and method disclosed herein have Effect aggregation Gram-negative oral bacteria.In some embodiments, using according to the patient of the composition of method 1 or method 2 Confirm that there are in mucus actinomyces, Lactobacillus casei, Streptococcus oralis, small veillonellasp and Fusobacterium nucleatum in its oral cavity It is one or more.In some embodiments, thin using oral cavity has been diagnosed according to the patient of the composition of method 1 or method 2 Bacterial diseases or illness, such as by mucus actinomyces, Lactobacillus casei, Streptococcus oralis, small veillonellasp and Fusobacterium nucleatum In it is one or more caused by oral bacterial infections.In some embodiments, using the trouble according to method 1 or 2 composition Person is with situation or from making it tend to oral bacterial infections (such as periodontitis, gingivitis, oral surgery, extraction, root pipe Treatment) treatment in restore, the oral bacterial infections are for example by the infection of Gram-negative bacteria, or pass through mucus unwrapping wire One or more infection in bacterium, Lactobacillus casei, Streptococcus oralis, small veillonellasp and Fusobacterium nucleatum.

In some embodiments, method 1 or 2 additionally provides reduction and inhibits the acid attack of enamel, cleaning tooth, reduces Biomembrane and patch, reduction gingivitis, inhibition saprodontia and the dental cavity formation and reduce the effective of hypersensitive dentin that bacterium generates Property.In one aspect, method 1 or 2 is used in combination with tooth brushing regimen so that scrub is from oral cavity structure (for example, tooth and tooth Gum) in evict oral bacteria from, and thus this method helps to assemble and remove these and evicts bacterium with free floating from.At some In embodiment, this method allows before oral bacteria can be re-adhered to the solid structure in oral cavity, temporary from oral surfaces The aggregation and destruction of the oral bacteria (for example, bacterial biof iotalm of tooth) of release.

In some embodiments, this disclosure provides the method according to method 1 or 2, for one kind in following Or a variety of is effective：(i) hypersensitivity of tooth is reduced, (ii) reduces Plaques form, and (iii) reduces or inhibit demineralization And promotes the Mineralization again of tooth, (iv) that the microbial biofilm in oral cavity is inhibited to be formed, (v) reduce or inhibit gum Inflammation, (vi) promote the healing of ulcer or notch in oral cavity, (vii) to reduce the level of acidogenic bactria, and (viii) increases non-cariogenic And/or non-patch forms the relative level of bacterium, (ix) is reduced or is inhibited the formation of saprodontia, (x) reduce, repair or inhibit tooth enamel It is corroded before the dental caries of matter, such as measured (ECM) detection by quantitative light induced fluorescence (QLF) or electric dental caries, (xi) treatment is alleviated Or dry is reduced, (xii) cleans tooth and oral cavity, and (xiii), which is reduced, to be corroded, (xiv) whitening teeth；(xv) accumulation of tartar is reduced, (xvi) fresh breath and/or treatment or prevention halitosis, and/or it includes cardiovascular health that (xvii), which promotes whole body health, for example (,) it is logical The possibility for reducing the general infection via oral cavity tissue is crossed, it is as above the method includes applying to the oral cavity of individual in need Any one of described composition 1 etc., such as be carried out one or more times a day.The present disclosure also provides in these methods It is any in composition 1 etc..

The present disclosure also provides oral care composition (such as the compositions 1 comprising metal-aminoacid complex Deng) promotion oral bacteria assembles and/or the purposes (purposes 1) of the immune clearance of promotion oral bacteria.In some embodiments, group Close object 1 it is equal promote the aggregation of oral bacteria and/or the purposes of immune clearance effectively treat mouth disease, illness or situation (such as Gingivitis, periodontitis, halitosis, dental cavity formation, enamel corrode or mouth infection) or destroy patch and bacterial biof iotalm shape At.In a particular embodiment, the purposes effectively reduces and inhibits the acid attack of enamel, cleaning tooth, reduces bacterium generation Biomembrane and patch, reduce gingivitis, inhibit decayed tooth and dental cavity formation, and/or reduce dentine hypersensitivity.In some realities It applies in example, the purposes executes patient in need, such as confirms there is mucus actinomyces, cheese breast bar in its oral cavity One or more existing patients in bacterium, Streptococcus oralis, small veillonellasp and Fusobacterium nucleatum, or diagnosis have mouth Chamber bacterial disease or illness, such as by mucus actinomyces, Lactobacillus casei, Streptococcus oralis, small veillonellasp and tool core shuttle The patient of one or more caused oral bacterial infections in bacillus.

In a particular embodiment, purposes 1 includes using according in the oral care composition of composition 1 or 1.1-1.45 Any purposes.In a particular embodiment, purposes 1 further includes：

1.1 purposes 1, wherein metal-aminoacid complex are zinc (II)-amino acid complex or copper (II)-amino acid network Close object.

1.2 purposes 1 or 1.1, wherein amino acid are basic amino acids.

1.3 any aforementioned applications, wherein amino acid are selected from lysine, glycine, trimethylglycine and arginine.

1.4 any aforementioned applications, wherein metal-aminoacid complex also include halide, such as chloride.

1.5 any aforementioned applications, wherein complex compound are zinc-lysine-chloride complex or zinc-ARGININE HYDROCHLORIDE network Close object.

1.6 any aforementioned applications, wherein complex compound are with chemical constitution [Zn (C₆H₁₄N₂O₂)₂Cl]⁺Cl^-Zinc lysine Chloride complex, or in cationic cation (such as [Zn (C₆H₁₄N₂O₂)₂Cl]⁺) and the solution of cl anion in, or with Solid salt form, optionally with monohydrate or dihydrate form.

1.7 any aforementioned applications, the wherein amount of zinc are 0.05-4% by weight.

1.8 any aforementioned applications, wherein composition are toothpaste, gel, mouthwash, powder, emulsifiable paste, item or chewing gum shape Formula.

1.9 any aforementioned applications, wherein composition are the form of mouthwash.

1.10 any aforementioned applications, wherein the purposes is effective treatment mouth disease, illness or situation (such as gum Inflammation, periodontitis, halitosis, dental cavity formation, enamel corrode or mouth infection) or destroy patch and bacterial biof iotalm formation.

The oral care composition used in present disclosure can be any oral care formulations form, including toothpaste, Gel, mouthwash, powder, emulsifiable paste, item, chewing gum or any other form known in the art.In some embodiments, this public affairs It is mouthwash to open the oral care composition used in content.

On the other hand, this disclosure provides metal-aminoacid complex such as zinc-amino acid complex or Purposes of the copper-amino acid complex in manufacturing for the oral care composition of method 1 or method 2, such as promoting mouth The aggregation of chamber bacterium and/or the immune clearance for promoting oral bacteria.As described elsewhere herein, this purposes is for treatment And/or it may be beneficial to prevent mouth disease or illness caused by the oral bacteria.Such metal-aminoacid complexing Object relies including those of description from beginning to end herein, such as zinc-amino acid complex, zinc-amino acid-halide complex, zinc- Propylhomoserin-halide complex, zinc-arginine halide complex, zinc-lysine-chloride complex and zinc-arginine-chlorine Compound complex compound.In a particular embodiment, such complex compound is zinc-lysine-chloride complexing of referred to herein as ZLC Object, such as with chemical constitution [Zn (C₆H₁₄N₂O₂)₂Cl]⁺The zinc LYSINE MONOHYDROCHLORIDE complex compound of Cl-, or cation (such as [Zn(C₆H₁₄N₂O₂)₂Cl]⁺) and the solution of cl anion in, or with solid salt form, such as crystal form, optionally with a water Close object or dihydrate form.Thus, for example, this disclosure provides ZLC, such as with chemical constitution [Zn (C₆H₁₄N₂O₂)₂Cl]⁺Cl^-Oral care composition of the zinc LYSINE MONOHYDROCHLORIDE complex compound in manufacture for method 1 or method 2 In purposes, such as aggregation for promoting oral bacteria and/or the immune clearance for promoting oral bacteria.

On the other hand, the present disclosure also provides such as zinc-amino of the metal-aminoacid complex for using The purposes of acid complex or copper-amino acid complex.As described elsewhere herein, this purposes is for treating and/or preventing Mouth disease or illness caused by the oral bacteria may be beneficial.According to method 1 or method 2, present disclosure is also Metal-aminoacid complex, such as zinc-amino acid complex are provided for promoting oral bacteria to assemble and/or promote oral cavity The purposes of the immune clearance of bacterium.Such metal-aminoacid complex includes those of description from beginning to end herein, such as Zinc-amino acid complex, zinc-amino acid-halide complex, zinc-lysine-halide complex, zinc-arginine halide Complex compound, zinc-lysine-chloride complex and zinc-arginine-chloride complex.In a particular embodiment, such network Zinc-lysine-chloride complex that object is referred to herein as ZLC is closed, such as with chemical constitution [Zn (C₆H₁₄N₂O₂)₂Cl]⁺Cl^-Zinc LYSINE MONOHYDROCHLORIDE complex compound, or in cationic cation (such as [Zn (C₆H₁₄N₂O₂)₂Cl]⁺) and chlorine the moon In the solution of ion, or with solid salt form, such as crystal form, optionally with monohydrate or dihydrate form.Therefore, For example, according to method 1 or method 2, this disclosure provides ZLC, such as with chemical constitution [Zn (C₆H₁₄N₂O₂)₂Cl]⁺Cl^- Zinc LYSINE MONOHYDROCHLORIDE complex compound be used for promote oral bacteria aggregation and/or promote oral bacteria immune clearance use On the way.

In some embodiments, it is anti-to may also include application for method disclosed herein and purposes (method 1, method 2 and purposes 1) Microbial inoculum, the collaboration to provide antimicrobial effect increase.This synergistic effect can arise from metal-aminoacid complex and promote bacterial accumulation With the ability of biofilm disruption, therefore increase antiseptic close to bacterial cell ability.Any antiseptic disclosed herein is equal It can be used for the synergistic effect, including but not limited to quaternary ammonium compound (such as pyrisept), halogenation hexichol Ether (such as triclosan) and extract of magnolia (such as magnolol, honokiol).

Oral care composition for present disclosure may include metal-aminoacid complex or may include its precursor. For example, when metal-aminoacid complex is zinc-amino acid-halide complex, it can be with water reaction in-situ to form zinc amino The precursor of acid halide complex compound includes：(i) zinc and amino acid hydrohalide, or (ii) zinc chloride and amino acid, or (iii) zinc Ion source, amino acid and hydracid, or (iv) (i), (ii) and/or (iii) combination.In one embodiment, zinc and amino-acids halogen Compound can be prepared by mixing precursor in solution such as water at room temperature.The easiness for providing preparation is formed in situ.It can It necessarily is formed using precursor rather than first zinc and amino-acids halide.In another embodiment, allow from the preceding bodily form into zinc ammonia The water of base acid halide is from the saliva and/or flushing water contacted after the application with composition.

Amino acid in the metal-aminoacid complex for the oral care composition that can be used for using in present disclosure Example includes but not limited to common natural amino acid, such as：Lysine, arginine, histidine, glycine, serine, Soviet Union's ammonia Acid, asparagine, glutamine, cysteine, selenocysteine, proline, alanine, valine, isoleucine, bright ammonia Acid, methionine, phenylalanine, tyrosine, tryptophan, aspartic acid and glutamic acid.In some embodiments, during amino acid is Property or acidic amino acid, such as glycine.In some embodiments, amino acid is Alkylation of Amino Acids, such as three-N- alkylations Amino acid, such as trimethylglycine.

When complex compound is formed by basic amino acid, metal-aminoacid complex such as zinc-amino acid complex promotes mouth The ability of chamber bacterial accumulation is most significant." basic amino acid " means naturally occurring basic amino acid, such as arginine, relies Any basic amino acid with carboxyl and amino in propylhomoserin and histidine and molecule, is water-soluble and offer has About 7 or bigger pH aqueous solution.Correspondingly, basic amino acid includes but not limited to arginine, lysine, citrulling, bird ammonia Acid, creatine, histidine, diaminobutyric acid, diaminopropionic acid, its salt or combinations thereof.In certain embodiments, amino acid is to rely ammonia Acid.In other embodiments, amino acid is arginine.

Halide can be chlorine, bromine or iodine, most typically be chlorine.The sour addition of amino acid and hydracid (such as HCl, HBr or HI) Salt is sometimes referred to as amino acid hydrohalide herein.Therefore an example of amino acid hydrohalide is lysine hydrochloride.Separately One is glycine hydrochloride.

In certain embodiments, the amount of the zinc and amino-acids halide in the oral care composition used in present disclosure For 0.05 to 10% based on the weight of composition.In certain embodiments, precursor such as zinc and amino acid hydrohalide are in this way Amount exist so that when being combined into zinc and amino-acids halide, zinc and amino-acids halide by based on the weight of composition 0.05 to 10% amount exists.These embodiments it is any in, the amount of zinc and amino-acids halide can change for the required purposes, such as Denfifrice or mouthwash.In other embodiments, the amount of zinc and amino-acids halide is based on the weight of composition at least 0.1, extremely Few 0.2, at least 0.3, at least 0.4, at least 0.5, at least 1, at least 2, at least 3 or at least 4 until 10%.In other embodiments In, the amount of amino acid zinc halide be less than 9 based on the weight of composition, less than 8, less than 7, less than 6, less than 5, less than 4, be less than 3, it is less than 2, is less than 1, is less than 0.5 to 0.05%.In other embodiments, the amount be based on the weight of composition 0.05 to 5%, 0.05 to 4%, 0.05 to 3%, 0.05 to 2%, 0.1 to 5%, 0.1 to 4%, 0.1 to 3%, 0.1 to 2%, 0.5 to 5%, 0.5 to 4%, 0.5 to 3% or 0.5 to 2%.

In certain embodiments, zinc is present in present disclosure by based on the weight of composition 0.05 to 10% amount and is made In oral care composition.In other embodiments, the amount of zinc be based on the weight of composition at least 0.1, at least 0.2, At least 0.3, at least 0.4, at least 0.5, at least 1, at least 2, at least 3 or at least 4 until 10%.In other embodiments, zinc Amount for based on the weight of composition be less than 9, be less than 8, be less than 7, be less than 6, be less than 5, be less than 4, be less than 3, be less than 2, be less than 1, it is small In 0.5 to 0.05%.In other embodiments, the amount is 0.05 to 5% based on the weight of composition, 0.05 to 4%, 0.05 To 3%, 0.05 to 2%, 0.1 to 5%, 0.1 to 4%, 0.1 to 3%, 0.1 to 2%, 0.5 to 5%, 0.5 to 4%, 0.5 to 3% or 0.5 to 2%.

In certain embodiments, amino acid hydrohalide is present in present disclosure with by weight 0.05 to 30% amount In the middle oral care composition used.In other embodiments, the amount be by weight at least 0.1, at least 0.2, at least 0.3, at least 0.4, at least 0.5, at least 1, at least 2, at least 3, at least 4, at least 5, at least 10, at least 15, at least 20 until 30%.In other embodiments, the amount be based on the weight of composition be less than 30, be less than 25, be less than 20, be less than 15, be less than 10, Less than 5, it is less than 4, is less than 3, is less than 2 or is less than 1 time to less than 0.05%.

When, there are when precursor material, they are preferably raw with approximation in the oral care composition used in this disclosure The molar ratio that zinc and amino-acids halide needed for production needs exists, although a kind of excessive material or another material are in certain systems It may be desired in agent, such as pH is balanced to be directed to other preparation constituents, provide other antimicrobial zinc, or provide amino Acid buffering agent.It is preferable, however, that the amount of halide is limited, because the horizontal of limitation halide slightly promotes zinc and amino Interaction between acid.

In some embodiments, the total amount of zinc is by composition in the oral care composition used in present disclosure Weight meter 0.05 to 8%.In other embodiments, the total amount of zinc be based on the weight of composition at least 0.1, at least 0.2, at least 0.3, at least 0.4, at least 0.5 or at least 1 until 8%.In other embodiments, the total amount of zinc is by composition in composition Weight meter be less than 5, be less than 4, be less than 3, be less than 2 or be less than 1 to 0.05%.

In certain embodiments, the molar ratio of zinc/amino acid is in the oral care composition used in present disclosure At least 2: 1.In other embodiments, molar ratio be at least 1: 1, at least 1: 2, at least 1: 3, at least 1: 4,2: 1 to 1: 4,1: 1 to 1: 4,1: 2 to 1: 4,1: 3 to 1: 4,2: 1 to 1: 3,2: 1 to 1: 2,2: 1 to 1: 1 or 1: 3.Zinc is expected higher than 1: 4 will be completely molten Solution.

In certain embodiments, the oral care composition used in present disclosure is anhydrous.Anhydrous is by weight Meter less than 5% water, optionally by weight be less than 4, less than 3, less than 2, less than 1, less than 0.5, less than 0.1 down toward 0% water.

Carrier in the oral care composition used in present disclosure, which represents, removes zinc and amino-acids halide in composition All other material outside complex compound or its precursor.Then include the weight of the zinc and amino-acids halide of any precursor by addition Amount, carrier amount reach 100%.

Activating agent：The oral care composition used in present disclosure may include that various activating agents, the activating agent are used In the intensity and integrality for protecting and enhancing enamel and tooth structure and/or reduce bacterium and relevant saprodontia and/or gum Disease, including or plus zinc-metal-halide complex compound.The effective concentration of active constituent used herein will depend on institute The particular agent and delivery system used.It should be understood that for example, toothpaste is diluted with water when will typically be in use, and mouth Portion's cleaning solution will not typically be diluted with water.Therefore, the effective concentration of activating agent will be usually oral area cleaning solution institute in toothpaste 5-15 times of the concentration needed.Concentration will also depend on selected exact salt or polymer.For example, providing work in the form of salts Property agent in the case of, counter ion counterionsl gegenions will influence the weight of salt, so that if counter ion counterionsl gegenions are heavier, will need by weight more More salt provides the active ion of same concentrations in the final product.When it is present, arginine can be with for example, about 0.1 to about 20 Weight % (weight for being expressed as free alkali), such as about 1 to about 10 weight % of consumer's toothpaste, or for profession or place The horizontal of about 7 to about 20 weight % of square treatment product exists.When it is present, fluoride can with for example, about 25 to about 25,000ppm, Such as consumer's toothpaste about 750 to about 2,000ppm, or for profession or prescribed treatment product about 2,000 to about 25, The horizontal of 000ppm exists.The level of antiseptic can similarly change, and the level wherein used in toothpaste is for example than in mouthwash High about 5 to about 15 times used.For example, triclosan toothpaste contains the triclosan of about 0.3 weight %.

Fluoride sources：The oral care composition used in present disclosure may also include one or more fluoride sources, Such as soluble fluoride salt dissolving.The substance that a variety of production fluorine ions can be used comes as the soluble fluoride in the present composition Source.The example of the substance of suitable production fluorine ion sees the U.S. Patent number 3,535,421 for authorizing Briner et al.；It authorizes The U.S. Patent number 4,885,155 of Parran, Jr et al. and the U.S. Patent number 3,678,154 for authorizing Widder et al..It represents Property fluoride sources include but not limited to stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, prodan, ammonium fluosilicate, amine Fluoride, ammonium fluoride and combinations thereof.In certain embodiments, fluoride sources include stannous fluoride, sodium fluoride, sodium monofluorophosphate and Its mixture.In certain embodiments, oral care composition as described herein also containing fluoride sources or provide fluorine at Point, present in an amount at least sufficient to the fluorine ion of supply about 25ppm to about 25,000ppm, is typically at least about 500ppm, for example, about 500 to about 2000ppm, for example, about 1000 to about 1600ppm, for example, about 1450ppm.The proper content of fluoride will depend on specific application. To typically have about 1000 to about 1500ppm for the toothpaste that ordinary consumer uses, wherein children's toothpaste is slightly lower.It is answered for profession Dentifrice or smears can be with the fluorides of up to about 5,000 or even about 25,000ppm.Fluoride sources can be Based on the weight of composition about 0.01 weight % is to about 10 weight % in one embodiment, or in another embodiment about 0.03 Weight % is to about 5 weight %, and the disclosure is added in the horizontal of about 0.1 weight % to about 1 weight % in another embodiment In the composition of content.The weight of the fluoride salt of fluorine ion for providing proper level will be based on the counter ion counterionsl gegenions in salt Weight meter significantly changes.

Abrasive material：The oral care composition used in present disclosure, for example, composition 1 etc. may include that silica is ground Material, and may include other abrasive material, such as calcium phosphate abrasive, such as tricalcium phosphate (Ca₃(PO₄)₂), hydroxyapatite (Ca₁₀ (PO₄)₆(OH)₂) or dicalcium phosphate dihydrate (CaHPO₄·2H₂O, herein otherwise referred to as DiCal) or calcium pyrophosphate； Calcium carbonate abrasive；Or abrasive material such as sodium metaphosphate, potassium metaphosphate, alumina silicate, calcined alumina, bentonite or other siliceous materials or A combination thereof.

Can be used for this paper other abrasive silica polishing materials and other abrasive materials generally have ranging from about 0.1 to About 30 microns, about 5 to about 15 microns of average particle size.Abrasive silica may be from precipitated silica or silica is solidifying Glue, such as in the U.S. Patent number 3,538,230 of authorizing Pader et al. and the U.S. Patent number 3,862 for authorizing Digiulio, Silica xerogel described in 307.Specific silica xerogel is by W.R.Grace＆Co.Davison Chemical Division is with trade (brand) nameIt sells.Precipitated silica material includes by J.M.Huber Corp. with trade (brand) nameThose of sell, include the silica with mark Zeodent 115 and 119.These abrasive silica Described in the U.S. Patent number 4,340,583 for authorizing Wason.In certain embodiments, it is used to prepare oral cavity as described herein The grinding-material of care composition includes silica gel and the amorphous silica of precipitation, and oil factor is less than about 100cc/100g bis- Silica and in the range of about 45cc/100g is to about 70cc/100g silica.Oil factor uses ASTA Rub-Out Method (wiping method) D281 are measured.In certain embodiments, silica is that have about 3 microns to about 12 microns and about 5 Micron to about 10 microns of average particle size colloidal particles.It is used in particular for preparing the low oil absorption silica of composition described herein Abrasive material is by W.R.Grace＆Co., and the Davison Chemical Division of Baltimore, Md.21203 are with trade name Sylodent It sells.Sylodent 650By the water content with by weight 29%, average diameter About 7 to about 10 microns and less than about 70cc/100g silica oil factor colloidal silica particles constitute titanium dioxide Silicone-hydrogel is the example for the low oil absorption silica abrasive that can be used in present disclosure practice.

Foaming agent：The oral care composition used in present disclosure may also include what increase was generated when scrubbing oral cavity The reagent of foam volume.The illustrative example for increasing the reagent of foam volume includes but not limited to polyoxyethylene and certain polymer, packet It includes but is not limited to alginate polymer.Polyoxyethylene can increase by the foam of the oral care carrier component generation of composition The thickness of amount and foam.Polyoxyethylene is generally referred to as polyethylene glycol (" PEG ") or polyethylene glycol oxide.It is suitable for the composition Polyoxyethylene by the molecular weight with about 200,000 to about 7,000,000.In one embodiment, molecular weight would be about 600,000 to about 2,000,000, and in another embodiment about 800,000 to about 1,000,000.Be by The trade (brand) name of the high molecular weight peo of Union Carbide productions.Polyoxyethylene can be by the mouth of oral care composition Chamber nurses the weight meter about 1% to about 90% of carrier component, and in one embodiment about 5% to about 50%, and at another The amount of about 10% to about 20% exists in embodiment.When it is present, in oral care composition foaming agent (i.e. single dose of amount Amount) it is by weight about 0.01 to about 0.9%, by weight about 0.05 to about 0.5%, and weight is pressed in another embodiment Gauge about 0.1 to about 0.2%.

Surfactant：Oral care composition for present disclosure can contain anion surfactant, such as：

I. the water soluble salt of higher fatty acids sulfate mono monoglyceride, for example, hydrogenated coconut fatty acid oil monosulfated list The sodium salt of glyceride, such as N- methyl Ns-cocoyl taurate, coconut oil monoglyceride sodium sulphate,

Ii higher alkyl sulfates, such as NaLS,

Iii. higher alkyl ether sulfates, for example, having formula CH₃(CH₂)_mCH₂(OCH₂CH₂)_nOSO₃X, wherein m are 6-16, Such as 10, n 1-6, such as 2,3 or 4, and X is Na or K, such as lauryl polyoxyethylene (2) ether sodium sulfate (CH₃(CH₂)₁₀CH₂(OCH₂CH₂)₂OSO₃Na)。

Iv. higher alkyl aryl sulfonates, such as neopelex (sodium lauryl benzene sulfonate)

V. higher alkyl sulfoacetates, such as lauryl sulfoacetate sodium (lauryl sulfoacetate sodium), 1,2 dihydroxy third High-grade aliphatic ester, the sulfolauric acid salt (sulfocolaurate) (N-2- Ethyl Lauroyl acid potassium sulfo groups acetamide) of alkyl sulfonic acid And sodium lauryl sarcosinate.

" senior alkyl " means such as C_6-30Alkyl.In a particular embodiment, anion surfactant is selected from bay Base sodium sulphate and sodium laureth sulfate.Anion surfactant can be effective (for example, more than 0.01 weight of formula Measure %), but be not at and there is the amount of (for example, being less than 10%) under the concentration for stimulating oral cavity tissue, and optium concentration depends on In special formulation and specific surfactant.For example, the concentration for mouthwash is typically used for the concentration of toothpaste about 1/10th.In one embodiment, anion surfactant with about 0.3 weight % to about 4.5 weight % (for example, about 1.5 Weight %) it is present in toothpaste.Oral care composition for present disclosure can the optionally mixing containing surfactant Object, such as comprising anion surfactant and can be anion, cation, amphoteric ion or non-ionic other surface-actives Agent.In general, surfactant is those of reasonably stability surfactant within the scope of wide pH.Surfactant is more fully Such as in the U.S. Patent number 3,959,458 for authorizing Agricola et al.；Authorize the U.S. Patent number 3,937,807 of Haefele； And it authorizes and is described more fully in the U.S. Patent number 4,051,234 of Gieske.In certain embodiments, it is applicable in this article Anion surfactant be included in alkyl with about 10 to about 18 carbon atoms alkyl sulfate water soluble salt with And the water soluble salt of the sulfonated monoglycerides of the aliphatic acid with about 10 to about 18 carbon atoms.NaLS, lauroyl Sodium sarcosinate and coco group coconut monoglyceride are the example of the anion surfactant of this type.It is specific at one In embodiment, compositions described herein, such as composition 1 etc. include NaLS.

The mixture of surfactant or compatible surfactant can be based on the weight of total composition about 0.1% to about 5.0%, in another embodiment about 0.3% to about 3.0%, and about 0.5% to about 2.0% deposit in another embodiment It is in composition as described herein.

Tartar control agents：In various embodiments, the oral care composition used in present disclosure may include anti-tooth Dirty agent (tartar control agents).Suitable anti-calculus agent include without limitation phosphate and Quadrafos (such as pyrophosphate), Poly- aminopropanesulfonic acid (AMPS), hexametaphosphate, Zinc citrate trihydrate, polypeptide, polyolefm sulfonates, polyolefin phosphoric acid Salt, diphosphate.Therefore the composition may include phosphate.In a particular embodiment, these salt are alkali metal phosphates, i.e. alkali The salt of metal hydroxides or alkaline earth metal hydroxide, such as sodium salt, sylvite or calcium salt.As used herein, " phosphate " Including orally acceptable monophosphate and polyphosphate, such as P_1-6Phosphate, such as monomer phosphate such as unitary phosphate, Binary phosphate or ternary phosphates；Two Quadrafos such as pyrophosphate；And polyphosphate, such as calgon.In spy In fixed example, selected phosphate is selected from alkali metal binary phosphate and alkali metal pyrophosphate, such as selected from phosphoric acid hydrogen two Sodium, dipotassium hydrogen phosphate, dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate and The mixture of any two in these or more.In a particular embodiment, such as composition includes tetrasodium pyrophosphate (Na₄P₂O₇), calcium pyrophosphate (Ca₂P₂O₇) and disodium hydrogen phosphate (Na₂HPO₄) mixture, for example, with the phosphoric acid hydrogen of about 3-4% The amount of each pyrophosphate of disodium and about 0.2-1%.In another embodiment, composition includes tetrasodium pyrophosphate (TSPP) With sodium tripolyphosphate (STPP) (Na₅P₃O₁₀) mixture, such as with the ratio of about 1-2%TSPP and about 7% to about 10%STPP Example.Such phosphate to help to clean tooth, and/or reduces tartar product can efficiently reduce the erosion of enamel Gather and provided in the amount on tooth, such as in terms of the weight of composition, in an amount of from 2-20%, such as about 5-15%.

Polymer：The oral care composition used in present disclosure may also include other polymer, to adjust system The viscosity of agent or the solubility of the other ingredients of enhancing.Such other polymer includes polyethylene glycol, (such as cellulose spreads out polysaccharide Biology, such as carboxymethyl cellulose；Or polysaccharide gum, such as xanthans or carrageenan).Acidic polymer (such as polyacrylic acid Gels) it can be carried in the form of its free acid or the water-soluble alkali partially or completely neutralized (such as potassium and sodium) or ammonium salt For.

Polymer architecture is formed in an aqueous medium or the silicon dioxide thickening agents of gel may be present in present disclosure In the oral care composition used.Notice that these silicon dioxide thickening agents are different from existing in group on physics and function The silica particle abrasive material in object is closed, because silicon dioxide thickening agents very finely separate and provide seldom abrasive action Or without the other thickeners of abrasive action it is carboxyl vinyl polymer, carrageenan, hydroxyethyl cellulose and cellulose ether Water soluble salt, such as sodium carboxymethylcellulose and carboxymethyl hydroxyethyl cellulose sodium.Also natural gum such as thorn Chinese parasol tree tree can be mixed Glue, gum arabic and gum tragacanth veegum also are used as the component of thickener composition, are combined with further improvement The quality of object.In certain embodiments, using by the thickener of the amount of about 0.5% to about 5.0% based on the weight of total composition.

Oral care composition for present disclosure may include anionic polymer, such as with about 0.05 to about 5% Amount.This kind of reagent that can be used for composition described herein is disclosed in U.S. Patent number 5,188,821 and 5,192,531；And And include the anionic polymerisation multi-carboxylate of synthesis, such as maleic anhydride or maleic acid and another polymerizable olefinic unsaturation 1: 4 to 4: 1 copolymer of monomer, preferred molecular weight (M.W.) are about 30,000 to about 1,000,000, most preferably from about 300,000 To about 800,000 methyl vinyl ether/maleic anhydride.These copolymers can be obtained for example as Gantrez, for example, can obtain From ISP Technologies, Inc., AN 139 (M.W.500,000), the AN 119 of Bound Brook, N.J.08805 (M.W.250,000) and preferred S-97 pharmaceutical grades (M.W.700,000).Reinforcing agent is when it is present with ranging from by weight about The amount of 0.05 to about 3% exists.Other polymer to work include such as maleic anhydride and ethyl acrylate, methacrylic acid Those of 1: 1 copolymer of hydroxyl ethyl ester, n-vinyl-2-pyrrolidone or ethylene, the latter can for example be compiled with Monsanto EMA Numbers 1103, M.W.10,000 and EMA class 6s 1 obtain；And acrylic acid and methyl methacrylate or hydroxyethyl methacrylate second 1: 1 copolymer of ester, methyl acrylate or ethyl acrylate, isobutylvinyl ether or n-vinyl-2-pyrrolidone.

Water：The oral care composition used in present disclosure may include the water of the level of signifiance.For business oral cavity group The water for closing the preparation of object should be deionized and be free of organic impurities.The water of the amount includes added free water in composition In addition the water for the amount being concomitantly introduced into other materials.

Moisturizer：In certain embodiments, also it is desirable to be mixed in the oral care composition used in this disclosure Moisturizer, to prevent composition from being hardened when being exposed to air.Certain moisturizer can also assign dentifrice composition desired Sweet taste or flavor.Suitable moisturizer include edible polyalcohol for example glycerine, D-sorbite, xylitol, propylene glycol and its The mixture of its polyalcohol and these moisturizer.In some embodiments of composition described herein, main moisturizer is glycerine, It can be more than 25%, for example, 25-35%, about 30% it is horizontal exist, with 5% or less other moisturizer.

Unless otherwise stated, all percentages of the composition component otherwise provided in this specification are based on 100% Total composition or weight of formulation are by weight.

As used in the whole text, range is with each of being described in range the short hand notation being worth.Any value in range is all It can be selected as range end point.It is incorporated in addition, all references cited herein is incorporated by reference accordingly.If the disclosure In definition and the definition of cited bibliography clash, then be subject to the disclosure.

Unless specified otherwise herein, otherwise it is interpreted as herein with all percentages of place's expression other in the present specification and amount It refer to weight percent.Given amount is the effective weight meter based on material.

Example

Example 1

The General reactions for being used to form zinc-lysine-chloride complex (ZLC) are as follows：

ZnO+2 (lysine HCl) → [Zn (lysine)₂Cl]Cl·2H₂O(ZLC)

The ZnO of 2: 1 molar ratios: lysine HCl suspension was prepared with stirring in about 12 hours at room temperature.It will mixing Object centrifuges.1ml supernatants are transferred in NMR pipes.Then NMR pipes are placed in the closed test tube filled with ethyl alcohol and are used for crystal Growth.Many colourless cubic crystals are formed after a week.The crystal structure of ZLC crystal is determined by single crystal X-ray diffraction.It is this multiple The size of miscellaneous molecule is 1.7nm*7.8nm*4.3nm.In the complex compound, Zn cations are by two lysine ligands, tool Have and comes from NH₂The O atom of two N atoms and the carboxyl from equatorial plane of group.It shows square-pyramid of distortion Shape geometry, vertex position are occupied by Cl atoms.This new structure generates positive cationic portion, and Cl anion are tied with it It closes to form ion salt.

The laboratory of pure ZLC powder scales up synthesis：By 2 moles of lysine HCl at room temperature with stirring and dissolving In 1000ml deionized waters, 1 mole of solid ZnO is slowly added in lysine HCl solution with stirring, and is continued in room It is stirred overnight under temperature (about 12 hours).By aaerosol solution with high speed centrifugation 15 minutes.Supernatant is slowly poured into ethyl alcohol.Immediately Form precipitation.About 5-8ml ethyl alcohol is needed to obtain 1g powder.The alcohol solvent containing powder is filtered, and obtains canescence Powder.Powder is placed in 50 DEG C of baking ovens and is used for drying, and obtains the product of 88% yield.PXRD is confirmed and ZLC crystal Compared to the purity of ZLC powder.

The low pH of ZLC is prepared in alternative, is at room temperature dissolved lysine HCl (2 molar equivalent) with stirring In deionized water.Concentrated hydrochloric acid equal to about 0.5 molar equivalent is added in reaction mixture.Then into reaction mixture ZnO (1 molar equivalent) is added, and stirs mixture until being completely dissolved generation, usually in a few minutes to a few hours.Reaction PH be maintained at 6 or less.ZLC complex compounds can be maintained at subacidity pH (i.e. in the solution of clear final reacting mixture ＜ pH 7) under more than 3 months, and without ZnO precipitate.Alternatively, reaction mixture can be spray-dried to obtain ZLC powder, Or reaction mixture can be adjusted to close to neutrality pH (such as 6.8), and can concentration ZLC reaction mixtures it is slow The crystal salt of ZLC is detached when evaporation.

Example 2

What is presented in table 1A and 1B is the exemplary mouthwash formulations for containing ZLC as zinc-amino acid complex.

Table 1A

Table 1B

Example 3

Preparing has buccal cavity gel toothpaste of the ZLC as active constituent.Zinc ion concentration is about 0.5% (w/w).

Table 2

Example 4

Prepare as described in Table 3 includes zinc-lysine, 1450ppm fluorides and phosphatic exemplary dentifrice：

Table 3

Example 5

The aggregation of oral bacteria：The stimulated whole saliva from people volunteer is collected, and as in present disclosure It is described, with it is untreated compare (water), (0.2% zinc oxide or 0.1% zinc oxide/0.05% zinc citrate are mixed for metal salt solution Close object), amino acid solution (0.3% arginine, 1% arginine or 0.94% lysine) or metal-aminoacid complex solution (1.2% zinc-Lysine Complex, 1.33% zinc-arginine complex or 1% bronze medal-Lysine Complex) mixes.Solution is existed It is incubated 15 minutes in culture dish at room temperature, then shoots photo.For metal salt, each ware only shows undissolved and/or heavy The metal salt in shallow lake.For amino acid, compared with negative control, variation is not observed.For each metal-aminoacid complex The big aggregation in hole, material is slowly formed and is deposited to ware bottom.These results are obtained visually and under low power amplification Confirm.

Culture dish is replaced to repeat above-mentioned experiment using round bottom test tube.For 30 minutes in incubation period, each test tube Take pictures with the progress of 5 minutes intervals.These experimental verifications are only assembled greatly in the solution containing metal-aminoacid complex The time dependence of body is formed.

In order to confirm that the clustering phenomena observed is due to bacterial accumulation, the aggregation mediated with host cell is on the contrary, people's saliva Liquid sample is first by filtration sterilization (0.2 microns vacuum filter), to remove host cell, cell fragment, oral bacteria and big Protein.5 species mixture (mucus actinomyces, Lactobacillus casei, the oral cavities of common oral bacterium are added into the saliva sample Streptococcus, small veillonellasp and Fusobacterium nucleatum).The clustering phenomena observed in this experiment is tested with for whole saliva That observes is identical.

In order to which qualitative assessment is assembled, by sterile 0.9%NaCl of the Streptococcus oralis bacterial suspension in the culture tube of capping In culture medium.Different test samples is added into each pipe, and culture medium was monitored in 610nM by about one hour period The absorbance at place.Before settling under gravity, the bacterium of this size keeps suspending in the solution a few houres.This gives this molten The uniform dim or opacity of liquid can be quantified by measuring absorbance of the solution at 610nm.Bacterial accumulation causes carefully Fungus matter group block, this initially improves absorbance, is then the drastically decline in the absorptivity when bacterial components are precipitated out, leaves More and more transparent solution.Therefore, the reduction of absorbance shows the formation of aggregates of bacteria.As a result it is shown in the following table 4：

It is obtained the results show that into culture addition be free of additive, containing 1.5% arginine, 5% arginine, The test solution result experimentation of 0.94% lysine or 0.35% zinc chloride do not show considerable variation in OD (610nm) or Raising in OD (610nm).In contrast, lead to the of short duration of absorbance as the 1.33% zinc-arginine complex of additive It increases, reached peak value at about 28 minutes, be then to being remarkably decreased in absorbance at about 55 minutes.Similarly, 1.2% The use of zinc-Lysine Complex leads to the peak value of the absorbance at about 21 minutes, then for by about 55 minutes when it is notable under Drop.These results confirm that metal-aminoacid complex promotes the clear ability of oral bacteria rapid aggregation.Use mucus actinomyces Obtain it is even more significant as a result, and these be shown in the following table 5.Only using zinc-lysine or zinc-arginine complex In the case of, absorbance of the final testing result at 610nm is close to zero：

Although describing the present invention, ability about particular example (including carrying out currently preferred pattern) The technical staff in domain is it will be appreciated that there are the numerous modifications and displacement of system described above and technology.It will be appreciated that using other Embodiment, and structure and function modification can be carried out without departing from the scope of the invention.Therefore, the scope of the present invention It should be construed broadly as what is illustrated in appended claims.

Claims

1. a kind of method promoting oral bacteria aggregation and/or immune clearance, the method includes the oral administration packets to individual The step of oral care composition containing metal-aminoacid complex.

2. according to the method described in claim 1, the wherein described metal-aminoacid complex is zinc (II)-amino acid complex Or copper (II)-amino acid complex.

3. according to the method described in claim 1, the wherein described amino acid is basic amino acid.

4. according to the method described in claim 1, the wherein described amino acid be selected from lysine, glycine, trimethylglycine and Arginine.

5. according to the method described in claim 1, the wherein described metal-aminoacid complex also includes halide, such as chlorination Object.

6. according to the method described in claim 1, wherein described metal-amido complex compound is zinc-lysine-chloride complex Or zinc-ARGININE HYDROCHLORIDE complex compound.

7. according to the method described in claim 1, the wherein described complex compound is with chemical constitution [Zn (C₆H₁₄N₂O₂)₂Cl]⁺Cl^- Chlorination lysine-zn complex compound, or in cationic cation (such as [Zn (C₆H₁₄N₂O₂)₂Cl]⁺) and cl anion is molten In liquid, or with solid salt form, optionally with monohydrate or dihydrate form.

8. according to the method described in claim 6, the amount of the wherein described zinc is 0.05-4% by weight.

9. according to the method described in claim 1, the wherein described composition with toothpaste, gel, mouthwash, powder, emulsifiable paste, item or The form of chewing gum, such as in the form of mouthwash.

10. according to the method described in claim 1, wherein the method effectively treats mouth disease, illness or situation (such as tooth Oulitis, periodontitis, halitosis, dental cavity formation, enamel corrode or mouth infection) or destroy plaque and bacterial biof iotalm shape At.

11. a kind of method for treating mouth disease, illness or situation, the method includes to patient in need apply comprising The step of oral care composition of metal-aminoacid complex, to promote the aggregation and/or immune clearance of oral bacteria.

12. according to the method for claim 11, wherein the metal-aminoacid complex is zinc (II)-amino-acid complex Object or copper (II)-amino acid complex.

13. according to the method for claim 11, wherein the amino acid is basic amino acid.

14. according to the method for claim 11, wherein the amino acid is selected from lysine, glycine, trimethylglycine And arginine.

15. according to the method for claim 11, wherein the metal-aminoacid complex also includes halide, such as chlorine Compound.

16. according to the method for claim 11, wherein the complex compound is zinc-lysine-chloride complex or zinc-essence Histidine chloride complex compound.

17. according to the method for claim 11, wherein the complex compound is with chemical constitution [Zn (C₆H₁₄N₂O₂)₂Cl]⁺ Cl^-Chlorination lysine-zn complex compound, or in cationic cation (such as [Zn (C₆H₁₄N₂O₂)₂Cl]⁺) and cl anion In solution, or with solid salt form, optionally with monohydrate or dihydrate form.

18. according to the method for claim 17, wherein the amount of the zinc is 0.05-4% by weight.

19. according to the method for claim 11, wherein the composition is with toothpaste, gel, mouthwash, powder, emulsifiable paste, item Or the form of chewing gum, such as in the form of mouthwash.

20. according to the method for claim 11, wherein the mouth disease, illness or situation be selected from gingivitis, periodontitis, Halitosis, dental cavity formation, enamel corrodes or mouth infection.